Evidence for the ectopic synthesis of melanin in human adipose tissue

Manpreet Randhawa, Tom Huff , Julio C. Valencia, Zobair Younossi, Vikas Chandhoke, Vincent J. Hearing , Ancha Baranova

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes in retinal pigment epithelium (RPE) cells, in the inner ear and the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes.

In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using Real-Time PCR and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with LC/UV/MS determination of the PTCA derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U- 14 C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted.

We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that utilizes its anti-inflammatory and its oxidative damage absorbing properties.

We realize that our study raises more questions than it answers. Both the causes and the consequences of melanin production in adipose tissue remain unknown. One obvious candidate for the regulatory molecule is a-MSH, which is intimately connected both to melanogenesis and to energy homeostasis. Our future research will be aimed at developing an appropriate cellular system to allow the study of adipocytic melanogenesis in vitro and to explore the connection between melanogenesis and metabolic syndrome.

In conclusion, our study demonstrates for the first time that the biosynthesis of melanin takes place in visceral adipose tissue of morbidly obese subjects. Thus, we have uncovered an entirely new phenomenon never reported before. Further research into this area is warranted.

This research has been supported by a grant from the Thomas F. Jeffress and Kate Miller Jeffress Memorial Trust and by the Intramural Research Program of the National Cancer Institute at NIH . A.B. and M.R. are grateful to Shobha M. Gowder for initial technical assistance with the project and F. Otaizo for the help with the first round of RT-PCR experiments.